In the spirit of our blog’s title, this is the first of several posts to tackle the FDA’s controversial revisions to its regulations defining “intended use” and describing the evidence relevant to determining a product’s intended use.  This post covers the background—what has happened, and why it is important.  Subsequent posts will cover some of the substantive and procedural concerns that have been raised about the agency’s revisions.

“Intended use” is a critical concept in FDA law.  Whether a product is a drug or device subject to FDA oversight depends on the product’s intended use.  This is because the Federal Food, Drug, and Cosmetic Act (FDCA) defines drugs and devices as products “intended for use” in diagnosis, cure, mitigation, treatment or prevention of disease, or “intended to affect the structure or any function of the body.”  To give an example that the FDA has used, this means that when charcoal is sold as fuel it is not FDA-regulated, but when charcoal is intended for use as an emergency treatment for poisoning, it is a drug subject to FDA regulation.

But, equally important for understanding the current controversy over the FDA’s definition of “intended use,” intended use is also relevant to the agency’s regulation of products that are clearly drugs or devices within its jurisdiction.  As Nathan Cortez has analyzed in more detail here, and the FDA has explained in more detail here, intended use can play a role in determining when FDA-authorized drugs and devices are marketed in violation of the FDCA.  Under the FDA’s interpretation of its statute, when an FDA-authorized drug or device is intended for an unapproved use—that is, when a manufacturer engages in off-label promotion—that can lead to violations of the FDCA by causing a drug to be misbranded (or, in some cases, an unapproved new drug), and a device to be misbranded or adulterated.

In short, a product’s intended use is crucial for understanding whether the product is subject to FDA oversight at all; if so, what FDA requirements apply, and; when those requirements are violated.

So, what is intended use?

The FDA has long defined intended use as the “objective intent of the persons legally responsible for the labeling” of a product (21 CFR 201.128 and 801.4).  FDA regulations provide that the agency may rely on numerous sources as evidence of this “objective intent,” including “labeling claims, advertising matter, or oral or written statements by [the persons legally responsible for the product’s labeling] or their representatives,” as well as the “circumstances surrounding distribution.”  The regulations also provide, in their concluding sentence, that “if a manufacturer knows, or has knowledge of facts that would give him notice, that a drug [or device] introduced into interstate commerce by him is to be used for conditions, purposes, or uses other than the ones for which he offers it, he is required to provide adequate labeling for such a drug [or device] which accords with such other uses to which the article is to be put.”

This last piece of the definition, suggesting that a manufacturer’s knowledge that health care providers, patients, or consumers actually use a product in a particular way can be evidence of the manufacturer’s intent that the product be used that way, has long caused concern among industry.  Although FDA seems to have rarely relied on manufacturer knowledge as evidence of intended use, companies nevertheless have worried that any knowledge of off-label uses of their products put them at risk of an FDA enforcement action—and because off-label uses can be quite common, in some circumstances such knowledge may be difficult to avoid.

And what has the FDA done?

The relevance of manufacturer knowledge to determining intended use is now front-and-center because the FDA has revised that last sentence in its definition of intended use (although the final rule has not yet gone into effect).  In 2015, the FDA published a proposed rule that, among other things,* would have changed the definition of intended use by completely deleting the last sentence in the regulations—a change that many in industry would have welcomed.  But, in its final rule issued in January 2017, the FDA did not completely delete the controversial sentence.  Instead, the FDA explained that its proposal was misinterpreted as eliminating manufacturer knowledge as a source of evidence for determining intended use, which was not what the agency intended.  The agency meant to clarify that manufacturer knowledge, alone, would not usually be sufficient evidence that an approved product was intended for a new, unapproved use.  To that end, the final regulation revised the sentence about manufacturer knowledge to indicate that the FDA would use a “totality of the evidence” standard to determine a manufacturer’s objective intent, in line with what the FDA described in the preamble as its “longstanding position that . . . the Agency may look to any relevant source of evidence” (emphasis added), including manufacturer knowledge.

Since the FDA issued the final rule, stakeholders have objected to the final rule on both substantive—e.g., the FDCA does not authorize FDA to establish this “totality of the evidence” standard—and procedural—e.g., the final rule is not a “logical outgrowth” of the proposal—grounds.  In response, the Agency has delayed the effective date of the final rule until March 19, 2018, and extended the period for comments until July 18, 2017.   (Additionally, because the agency’s revisions were established during President’s Obama’s administration, the delayed effective date may give the new Commissioner time to consider the rule.)

That is where things stand, and in future posts I plan to comment on some of the really interesting substantive and procedural issues here.  In the meantime, for those interested in commenting on the controversy, the relevant information is here.

*N.B.: A primary focus of the rule is on a different—but also important—intended use issue: when products made or derived from tobacco are properly categorized as tobacco products, or as drugs, devices, or drug-device combination products, under the FDCA.